Neuropathology in Tourette Syndrome.

The unique clinical presentation of Tourette syndrome (TS) and its symptomatic response to dopamine antagonists are widely cited as evidence for the central role of the limbic-motor interface in the pathophysiology of TS. Nonetheless, the true neuropathology of TS remains elusive, even though significant advances have been made in understanding complex interconnected circuitries within the limbic system and basal ganglia. Neuropathologic and neuroimaging studies—plagued by small samples, clinical heterogeneity, and a number of interpretative problems—are generally supportive of pathology within the orbitofrontal cortex, striatum, and their efferent projections in TS. The specific patterns of abnormalities vary widely across these studies, clouding attempts to define a unifying neuropathology for this disorder. Converging yet circumstantial evidence for frontal cortical, and basal ganglia pathology in TS comes also from studies infields ranging from neuroimmunology to neuropsychology, and from the clinical overlap between TS and disorders such as obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, and Sydenhams chorea. As a “model” neuropsychiatric disorder, TS has stimulated advances in several areas of neurobiology research, yet we still await a real understanding of its pathophysiology in order to move from empirically driven therapeutics to the development of targeted effective treatments.